Mesangiolysis and/or mesangial cell proliferation are involved in the pathogenesis of several glomerular disease states in humans. The long-term goals of this project are to analyze the mechanistic events underlying these phenomena, particularly in terms of growth regulation of glomerular cells, cell-cell interactions and cell-matrix interactions. It has been found that heparin profoundly inhibits mesangial cell proliferation in vitro and in vivo. Heparin-like species also inhibit vascular smooth muscle cell proliferation, but there are differences and similarities in the responses of these two cell types. It will be established whether non-anticoagulant, (particularly antithrombotic), heparin-like species have similar effects. As in vivo, simple mesangial cell proliferative systems, the Habu snake venom, and nickel subsulfide, models will be used. The latter is also characterized by erythrocytosis. Mesangial cells are thought to produce erythropoietin. The effects of heparin-like species in these regards will also be studied, both in vivo and in vitro. Conditioned media from glomerular epithelial cells inhibit mesangial cell proliferation. Endothelial cells produce both inhibitory and stimulatory activities. These activities will be characterized, particularly as to whether the inhibitory activities represent heparin-like species. The mechanisms of mesangiolysis in the Habu snake venom model will be studied to establish whether the primary injury is cellular, or is on the mesangial matrix. If the latter, the interactions between the matrix and mesangial cells, in terms of cellular integrity will be investigated. The aminonucleoside of puromycin effects glomerular epithelial cells, both in vitro and in vivo, in the latter case producing a proteinuria and a lesion similar to lipoid nephrosis in children. Protective effects against the aminonucleoside have been found in vitro with various carbohydrate compounds, including heparin. Protection will be further characterized, particularly in regard to cell-matrix interaction mechanisms, and role of oxygen-free radicals in producing the lesion.